Author SummaryThe fusion of precursor cells is a crucial step in many biological processes, one of which is the development of skeletal muscle. The molecular and cell biology of fusion of muscle precursors has been well described in Drosophila melanogaster larvae, leading to insights into the process in vertebrates. However, the identity and mechanism of action of essential cell surface proteins for fusion between vertebrate muscle precursors has previously been lacking. Here, we describe a vertebrate-specific cell surface receptor pair that is essential for fusion in zebrafish: Jamb and Jamc. Loss of function of either receptor causes a near-complete block in fusion, resulting in an overabundance of mononucleate muscle fibres that are otherwise overtly normal. We demonstrate that Jamb and Jamc physically interact and are co-expressed by muscle precursors. Moreover, we show that the interaction between them is essential for fusion between neighbouring precursors in an embryo. We hypothesise that binding of Jamb to Jamc is a necessary recognition and adhesion step permissive for, but not sufficient to cause, myocyte fusion. Knowledge of these molecular components in vertebrates will lead to better understanding of how fusion is controlled to pattern skeletal muscle tissue.